Gpnmb silencing protects against hyperoxia-induced acute lung injury by inhibition of mitochondrial-mediated apoptosis.

Xiaoqin Wang, Song Qin, Yingcong Ren, Banghai Feng, Junya Liu, Kun Yu, Hong Yu, Zhenliang Liao, Hong Mei, Mei Tan
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Abstract

Background: Hyperoxia-induced acute lung injury (HALI) is a complication to ventilation in patients with respiratory failure, which can lead to acute inflammatory lung injury and chronic lung disease. The aim of this study was to integrate bioinformatics analysis to identify key genes associated with HALI and validate their role in H2O2-induced cell injury model.Methods: Integrated bioinformatics analysis was performed to screen vital genes involved in hyperoxia-induced lung injury (HLI). CCK-8 and flow cytometry assays were performed to assess cell viability and apoptosis. Western blotting was performed to assess protein expression.Results: In this study, glycoprotein non-metastatic melanoma protein B (Gpnmb) was identified as a key gene in HLI by integrated bioinformatics analysis of 4 Gene Expression Omnibus (GEO) datasets (GSE97804, GSE51039, GSE76301 and GSE87350). Knockdown of Gpnmb increased cell viability and decreased apoptosis in H2O2-treated MLE-12 cells, suggesting that Gpnmb was a proapoptotic gene during HALI. Western blotting results showed that knockdown of Gpnmb reduced the expression of Bcl-2 associated X (BAX) and cleaved-caspase 3, and increased the expression of Bcl-2 in H2O2 treated MLE-12 cells. Furthermore, Gpnmb knockdown could significantly reduce reactive oxygen species (ROS) generation and improve the mitochondrial membrane potential.Conclusion: The present study showed that knockdown of Gpnmb may protect against HLI by repressing mitochondrial-mediated apoptosis.

沉默 Gpnmb 可通过抑制线粒体介导的细胞凋亡防止高氧诱导的急性肺损伤。
背景:高氧诱导的急性肺损伤(HALI)是呼吸衰竭患者通气的并发症,可导致急性炎症性肺损伤和慢性肺部疾病。本研究旨在整合生物信息学分析,找出与 HALI 相关的关键基因,并验证它们在 H2O2- 诱导的细胞损伤模型中的作用:方法:通过综合生物信息学分析筛选出参与高氧诱导肺损伤(HLI)的重要基因。采用 CCK-8 和流式细胞术测定评估细胞活力和凋亡。采用 Western 印迹法评估蛋白质表达:本研究通过对 4 个基因表达总库(GEO)数据集(GSE97804、GSE51039、GSE76301 和 GSE87350)进行综合生物信息学分析,发现糖蛋白非转移性黑色素瘤蛋白 B(Gpnmb)是 HLI 的关键基因。在H2O2处理的MLE-12细胞中,敲除Gpnmb增加了细胞活力,减少了细胞凋亡,这表明Gpnmb是HALI过程中的促凋亡基因。Western blotting结果显示,在H2O2处理的MLE-12细胞中,敲除Gpnmb会降低Bcl-2相关X(BAX)和裂解-天冬酶3的表达,增加Bcl-2的表达。此外,Gpnmb敲除可显著减少活性氧(ROS)的产生,并改善线粒体膜电位:本研究表明,敲除 Gpnmb 可抑制线粒体介导的细胞凋亡,从而预防 HLI。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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